System and method to increase the overall diameter of veins

ABSTRACT

A system and method for increasing the speed of blood and wall shear stress (WSS) in a peripheral vein for a sufficient period of time to result in a persistent increase in the overall diameter and lumen diameter of the vein is provided. The method includes pumping blood at a desired rate and pulsatility. The pumping is monitored and adjusted, as necessary, to maintain the desired blood speed, WSS and pulsatility in the peripheral vein in order to optimize the rate and extent of dilation of the peripheral vein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to systems and methods for persistentlyincreasing the overall diameter and the lumen diameter of veins inpatients. Specifically, the present invention relates to systems andmethods that utilize a blood pump to increase the blood speed and wallshear stress (WSS) on the endothelium of peripheral veins for a periodof time that results in a persistent increase in the overall diameterand lumen diameter of those veins.

2. Background Information

Many patients with chronic kidney disease eventually progress toend-stage renal disease (ESRD) and need renal replacement therapy inorder to remove fluid and waste products from their body and sustaintheir life. Most patients with ESRD needing renal replacement therapyreceive hemodialysis. During hemodialysis, blood is removed from thecirculatory system, cleansed in a hemodialysis machine, and thenreturned to the circulatory system. Surgeons create discrete “vascularaccess sites” that can be used to remove and return blood rapidly fromESRD patients. While major advances have been made in the hemodialysismachines themselves and other parts of the hemodialysis process, thecreation of durable and reliable vascular access sites where blood canbe removed and returned to patients during hemodialysis sessions hasseen only modest improvement and remains the Achilles' heel of renalreplacement therapy. This often results in sickness and death for ESRDpatients and places a large burden on health care providers, payers, andpublic assistance programs worldwide.

Hemodialysis access sites generally come in three forms: arteriovenousfistulas (AVF), arteriovenous grafts (AVG), and catheters. Each type ofsite is susceptible to high rates of failure and complications, asdescribed below.

An AVF is constructed surgically by creating a direct connection betweenan artery and vein. A functional wrist AVF is the longest-lasting, mostdesirable form of hemodialysis access, with a mean patency of about 3years. The vein leading away from the connection is called the “outflow”vein. Dilation of the outflow vein is a critical component for an AVF to“mature” and become usable. It is widely believed that the rapid flow ofblood in the outflow vein created by the AVF and the WSS it exerts onthe endothelium of the vein is the major factor driving vein dilation.Unfortunately, approximately 80% of patients aren't eligible for AVFplacement in the wrist, usually due to inadequate vein diameter. Foreligible patients where AVF placement is attempted, the site is notusable without further intervention in about 50%-60% of cases, a problemknown as “maturation failure”. Small vessel diameter, especially smallvein diameter, has been identified as an important factor in AVFmaturation failure. The rapid appearance of aggressive vein wallscarring known as “intimal hyperplasia” has also been identified as animportant factor in AVF maturation failure. It is generally believedthat the turbulence created by the rapid flow of blood out of the arteryand into the vein is a major factor causing this vein wall scarring.Some investigators also postulate that cyclic stretching of the veincaused by the entry of pulsatile arterial blood may also play a role inthe stimulation of intimal hyperplasia and outflow vein obstruction inAVF. As such, there is a teaching that rapid flow is problematic, andattempts have been made to reduce flow in hemodialysis access sites byrestricting lumen diameter by banding in order to minimize failurerates. At the current time, no method exists which preserves positiveeffects of flow-mediated dilation while eliminating the negative effectsof vein wall scarring and obstruction. Not surprisingly, a patient newlydiagnosed with ESRD and in need of hemodialysis has only a 50% chance ofhaving a functional AVF within 6 months after starting hemodialysis.Those patients without a functional AVF are forced to dialyze with morecostly forms of vascular access and are at a greater risk ofcomplications, sickness, and death.

The second type of vascular access for hemodialysis is known as anarteriovenous graft (AVG). An AVG is constructed by placing a segment ofsynthetic conduit between an artery and vein, usually in the arm or leg.A portion of the synthetic conduit is placed immediately under the skinand used for needle access. More patients are eligible for AVGs, sinceveins not visible on the skin surface can be used for outflow, and therate of early failure is much lower than for AVFs. Unfortunately, AVGmean primary patency is only about 4-6 months, mostly because aggressiveintimal hyperplasia and scarring develops rapidly in the wall of thevein near the connection with the synthetic conduit, leading to stenosisand thrombosis. Similar to the situation with AVF failure, the rapid andturbulent flow of blood created by the AVG is thought to drive intimalhyperplasia and scarring in the wall of the outflow vein, oftenresulting in obstruction of the AVG. Some investigators also postulatethat cyclic stretching of the vein caused by the entry of pulsatilearterial blood may also play a role in the formation of intimalhyperplasia and outflow vein obstruction in AVG. Although AVGs are lessdesirable than AVFs, about 25% of patients dialyze with an AVG, mostlybecause they are not eligible to receive an AVF.

Patients who are not able to get hemodialysis through an AVF or AVG musthave a large catheter inserted in the neck, chest, or leg in order toreceive hemodialysis. These catheters often become infected, placing thepatient at high risk for sepsis and death. Patients with catheter sepsisusually require hospitalization, removal of the catheter, insertion of atemporary catheter, treatment with IV antibiotics, and then placement ofa new catheter or other type of access site when the infection hascleared. Catheters are also susceptible to obstruction by thrombus andfibrin build-up around the tip. Hemodialysis catheters have a meanpatency of about 6 months and are generally the least desirable form ofhemodialysis access. Although catheters are less desirable than AVFs andAVG, about 20% of patients dialyze with a catheter, mostly because theyhave not yet been able to receive a functional AVF or AVG, or are noteligible to receive an AVF or AVG.

The problem of hemodialysis access site failure has received moreattention recently as the number of ESRD patients undergoing routinehemodialysis has increased worldwide. In 2004, the Centers for Medicare& Medicaid Services (CMS) announced a “Fistula First” initiative toincrease the use of AVFs in providing hemodialysis access for patientswith end-stage renal failure. This major initiative is a response topublished Medicare data showing that patients who dialyze with an AVFhave reduced morbidity and mortality compared to patients with an AVG ora catheter. Costs associated with AVF patients are substantially lowerthan the costs associated with AVG patients in the first year ofdialysis, and in subsequent years. The cost savings of a dialyzing withan AVF are even greater when compared to dialyzing with a catheter.

To be eligible for an AVF or AVG, patients must have a peripheral veinwith a lumen diameter of at least 2.5 mm or 4 mm, respectively. However,there is currently no method for persistently increasing the overalldiameter and lumen diameter of peripheral veins in ESRD patients who areineligible for an AVF or AVG due to inadequate vein size. Consequently,patients with veins that are too small to attempt an AVF or AVG areforced to use less desirable forms of vascular access such as catheters.Similarly, there is currently no method of treatment for AVF maturationfailure, which falls disproportionately on patients with small veindiameters. Thus, systems and methods for enlarging the overall diameterand lumen diameter of a vein prior to the creation of AVF or AVG areneeded. The importance of this need is highlighted by a recent studydemonstrating that ESRD patients who were forced to use less desirableforms of vascular access such as catheters had a substantially higherrisk of becoming sick or dying when compared with patients who were ableto use an AVF or AVG for hemodialysis.

There is also a need to persistently increase vein diameter for otherpatients, such as those with atherosclerotic blockage of peripheralarteries who are in need of peripheral bypass grafting. Patients withperipheral artery disease (PAD) who have an obstruction to blood flow inthe arteries of the legs often suffer from claudication, skinulceration, and tissue ischemia and many of these patients eventuallyrequire amputation of portions of the affected limb. In some of thesepatients, the obstruction can be relieved to an adequate degree byballoon angioplasty or the implantation of a vascular stent. In manypatients, however, the obstruction is too severe for these types ofminimally invasive therapies. Therefore, surgeons will often create abypass graft that diverts blood around the obstructed arteries andrestores adequate blood flow to the affected extremity. However, manypatients in need of a peripheral bypass graft cannot use their own veinsas bypass conduits due to inadequate vein diameter and are forced to usesynthetic conduits made of materials such as polytetrafluoroethylene(PTFE, e.g. Gore-Tex) or polyethylene terephthalate (PET, e.g. Dacron).Studies have shown that using a patient's own veins as bypass conduitsresults in better long term patency than using synthetic bypass conduitsmade from materials such as PTFE or Dacron. The use of a syntheticbypass conduit increases the risk of stenosis in the artery at thedistal end of the graft and thrombosis of the entire conduit, resultingin bypass graft failure and a recurrence or worsening of symptoms. Thus,systems and methods for increasing the overall diameter and lumendiameter of veins prior to the creation of bypass grafts are needed,especially for patients who are ineligible to use their own veins forthe creation of a bypass graft due to inadequate vein diameter.

In view of the above, it will be apparent to those skilled in the artfrom this disclosure that there exists a need for a system and methodfor persistently increasing the lumen diameter and overall diameter ofperipheral veins so that those veins can be used for the creation ofhemodialysis access sites and bypass grafts. The invention describedherein addresses this need in the art as well as other needs, which willbecome apparent to those skilled in the art from this disclosure.

SUMMARY OF THE INVENTION

The present invention includes methods of using a blood pump to increasethe overall diameter and the lumen diameter of peripheral veins. Systemsand methods are described wherein the wall shear stress (WSS) exerted onthe endothelium of the peripheral vein is increased by placing a bloodpump upstream of the peripheral vein for a period of time sufficient toresult in dilation of the peripheral vein. The pump directs the bloodinto the peripheral vein preferably in a manner wherein the blood hasreduced pulse pressure when compared with the pulse pressure of blood ina peripheral artery.

Studies have shown hemodynamic forces and changes in hemodynamic forceswithin veins play a vital role in determining the overall diameter andlumen diameter of those veins. For example, persistent increases inblood speed and WSS can lead to vein dilation, with the amount ofdilation being dependent both on the level of increased blood speed andWSS and the time that the blood speed and WSS are elevated. The elevatedblood speed and WSS are sensed by endothelial cells, which triggersignaling mechanisms that result in stimulation of vascular smoothmuscle cells, attraction of monocytes and macrophages, and synthesis andrelease of proteases capable of degrading components of theextracellular matrix such as collagen and elastin. As such, the presentinvention relates to increasing blood speed and WSS for a period of timesufficient to result in vein remodeling and dilation, preferably for aperiod of time greater than seven days. The present invention alsorelates to methods of periodic adjustment of pump parameters to optimizevein remodeling and dilation.

Wall shear stress has been shown to be the key factor for blood vesseldilation in response to an increased blood flow. Assuming aHagen-Poiseuille blood flow in the vessel (i.e. a laminar flow with afully developed parabolic velocity profile), then WSS is given by theequation:WSS(τ)=4Qμ/πR ³, where:

-   -   Q=volume flow rate in mL/s    -   μ=viscosity of blood in units of poise    -   R=radius of vessel in cm    -   τ=wall shear stress in dynes/cm²

The systems and methods described herein increase the WSS level in aperipheral vein. Normal WSS for veins ranges between 0.076 Pa and 0.76Pa. The systems and methods described herein increase the WSS level to arange between 0.76 Pa and 23 Pa, preferably to a range between 2.5 Paand 7.5 Pa. Preferably, the WSS is increased for between 7 days and 84days, or preferably between 7 and 42 days, to induce persistent dilationin the peripheral accepting vein such that veins that were initiallyineligible for use as a hemodialysis access site or bypass graft due toa small vein diameter become usable. This can also be accomplished byintermittently increasing WSS during the treatment period, withintervening periods of normal WSS.

The systems and methods described herein also increase the speed ofblood in peripheral veins and in certain instances, peripheral arteries.At rest, the mean speed of blood in the cephalic vein in humans isgenerally between 5-9 cm/s, while the speed of blood in the brachialartery is generally between 10-15 cm/s. For the systems and methodsdescribed herein, the mean speed of blood in the peripheral vein isincreased to a range between 15 cm/s-100 cm/s, preferably to a rangebetween 25 cm/s and 100 cm/s, depending on the diameter of peripheralaccepting vein and the length of time the pumping of blood into theperipheral accepting vein is planned. Preferably, the mean blood speedis increased for between 7 days and 84 days, or preferably between 7 and42 days, to induce persistent dilation in the peripheral accepting veinsuch that veins that were initially ineligible for use as a hemodialysisaccess site or bypass graft due to a small vein diameter become usable.This can also be accomplished by intermittently increasing mean bloodspeed during the treatment period, with intervening periods of normalmean blood speed.

A method of increasing the lumen diameter and overall diameter of aperipheral vein in a patient is set forth herein. The method comprisesperforming a first procedure to access an artery or vein (the donatingvessel) and a peripheral vein (the accepting vein) and connecting thedonating vessel to the accepting vein with a pump system. The pumpsystem is then activated to artificially direct blood from the donatingvessel to the accepting vein. The method also includes monitoring theblood pumping process for a period of time. The method further includesadjusting the speed of the pump, the speed of the blood being pumped, orthe WSS on the endothelium of the accepting vein and monitoring thepumping process again. After a period of time has elapsed to allow forvein dilation, the diameter of the accepting vein is measured todetermine if adequate persistent increase in the overall diameter andlumen diameter of the accepting vein has been achieved and the pumpingprocess is adjusted again, as necessary, When adequate amount ofpersistent increase in the overall diameter and lumen diameter of theaccepting vein has been achieved, a second surgery is performed toremove the pump. A hemodialysis access site (such as an AVF or AVG) orbypass graft can be created at this time, or a later time, using atleast a portion of the persistently enlarged accepting vein.

In one embodiment, a surgical procedure is performed to expose segmentsof two veins. One end of a first synthetic conduit is “fluidly”connected (i.e. joined lumen to lumen to permit fluid communicationtherebetween) to the vein where blood is to be removed (the donatingvein). The other end of the first synthetic conduit is fluidly connectedto the inflow port of a pump. One end of a second synthetic conduit isfluidly connected to the vein where blood is to be directed (theaccepting vein). The other end of the second synthetic conduit isfluidly connected to the outflow port of the same pump. Deoxygenatedblood is pumped from the donating vein to the accepting vein until thevein has persistently dilated to the desired overall diameter and lumendiameter. The term “persistently dilated” is used herein to mean thateven if a pump is turned off an increase in overall diameter or lumendiameter of a vessel can still be demonstrated, when compared to thediameter of the vein prior to the period of blood pumping. That is, thevessel has become larger independent of the pressure generated by thepump. Once the desired amount of persistent vein enlargement hasoccurred, a second surgical procedure is performed to remove the pumpand synthetic conduits. A hemodialysis access site (such as an AVF orAVG) or bypass graft can be created at this time, or a later time, usingat least a portion of the persistently enlarged accepting vein. In thisembodiment, the pump port may be fluidly connected directly to thedonating vein or the accepting vein without using an interposedsynthetic conduit. In a variation of this embodiment, the accepting veinmay be located in one body location, such as the cephalic vein in an armand the donating vein may be in another location, such as the femoralvein in a leg. In this instance, the two ends of the pump-conduitassembly will be located within the body and a bridging portion of thepump-conduit assembly may be extracorporeal (outside the body, e.g. wornunder the clothing) or intracorporeal (inside the body, e.g. tunneledunder the skin). Furthermore, in certain instances, the donating vesselmay be more peripheral in relative body location than the acceptingvein.

In another embodiment, a method comprises a surgical procedure that isperformed to expose a segment of a peripheral artery and a segment of aperipheral vein. One end of a first synthetic conduit is fluidlyconnected to the peripheral artery. The other end of the first syntheticconduit is fluidly connected to the inflow port of a pump. One end of asecond synthetic conduit is fluidly connected to the peripheral vein.The other end of the second synthetic conduit is fluidly connected tothe outflow port of the same pump. Pumping oxygenated blood from theperipheral artery to the peripheral vein is performed until the vein haspersistently dilated to the desired overall diameter and lumen diameter.Once the desired amount of vein enlargement has occurred, a secondsurgical procedure is performed to remove the pump and syntheticconduits. A hemodialysis access site (such as an AVF or AVG) or bypassgraft can be created at this time, or a later time, using at least aportion of the persistently enlarged accepting vein. A variation of thisembodiment is provided wherein the pump port may be fluidly connecteddirectly to the artery or vein without using an interposed syntheticconduit.

In yet another embodiment, a pair of specialized catheters are insertedinto the venous system. The first end of one catheter is attached to theinflow port of a pump (hereafter the “inflow catheter”) while the firstend of the other catheter is attached to the outflow port of the pump(hereafter the “outflow catheter”). Optionally, the two catheters can bejoined together, such as with a double lumen catheter. The catheters areconfigured for insertion into the lumen of the venous system. Afterinsertion, the tip of the second end of the inflow catheter ispositioned in anywhere in the venous system where a sufficient amount ofblood can be drawn into the inflow catheter (e.g. the right atrium,superior vena cava, subclavian vein, or brachiocephalic vein). Afterinsertion, the tip of the second end of the outflow catheter ispositioned in a segment of peripheral vein (the accepting vein) in thevenous system where blood can be delivered by the outflow catheter (e.g.cephalic vein). The pump then draws deoxygenated blood into the lumen ofthe inflow catheter from the donating vein and discharges the blood fromthe outflow catheter and into the lumen of the accepting vein. In thisembodiment, the pump and a portion of the inflow catheter and outflowcatheters remain external to the patient. The pump is operated until thedesired amount of persistent overall diameter and lumen diameterenlargement has occurred in the accepting vein, whereupon the pump andcatheters are removed. A hemodialysis access site (such as an AVF orAVG) or bypass graft can be created at this time, or a later time, usingat least a portion of the persistently enlarged accepting vein.

A system for increasing the blood speed and WSS in a vein by delivery ofdeoxygenated blood from a donating vein to an accepting vein in apatient is provided that comprises two synthetic conduits, each with twoends, a blood pump, a control unit, and a power source. This system mayalso contain one or more sensor units. In one embodiment of the system,the synthetic conduits and pump, collectively known as the “pump-conduitassembly” is configured to draw deoxygenated blood from the donatingvein or the right atrium and pump that blood into the accepting vein.The pump-conduit assembly is configured to pump deoxygenated blood. Inanother embodiment of the system, the pump-conduit assembly isconfigured to draw oxygenated blood from a peripheral artery and pumpthe blood into a peripheral vein. The blood is pumped in a manner thatincreases the blood speed in the artery and vein and increases WSSexerted on the endothelium of the artery and vein for a period of timesufficient to cause a persistent increase in the overall diameter andlumen diameter of the peripheral artery and vein. Preferably, the bloodbeing pumped into peripheral vein has low pulsatility, for example lowerpulsatility than the blood in a peripheral artery. A variation of thisembodiment is provided whereby the pump is fluidly connected directly tothe artery or vein (or both) without using an interposed syntheticconduit. The pump includes an inlet and an outlet, and the pump isconfigured to deliver deoxygenated or oxygenated blood to the peripheralvein in a manner that increases the speed of the blood in the vein andthe WSS exerted on the endothelium in the vein to cause a persistentincrease in the overall diameter and the lumen diameter of theperipheral vein. The blood pump may be implanted in the patient, mayremain external to the patient, or may have implanted and externalportions. All or some of the synthetic conduits may be implanted in thepatient, may be implanted subcutaneously, or may be implanted within thelumen of the venous system, or any combination thereof. The implantedportions of pump-conduit assembly may be monitored and adjustedperiodically, for example, every seven days.

The invention includes methods of increasing the blood speed in aperipheral vein and increasing the WSS exerted on the endothelium of aperipheral vein of a human patient in need of a hemodialysis access siteor a bypass graft are also provided. A device designed to augmentarterial blood flow for the treatment of heart failure would be usefulfor this purpose. Specifically, a ventricular assist device (VAD) whichis optimized for low blood flows would be capable of pumping blood froma donating vessel to a peripheral vein to induce a persistent increasein overall diameter and lumen diameter of the peripheral vein. Invarious embodiments, a pediatric VAD, or a miniature VAD designed totreat moderate heart failure in adults (such as the Synergy pump byCirculite) may be used. Other devices, including an LVAD or an RVAD thatare optimized for low blood flows, may also be used.

The method comprises fluidly connecting the low-flow VAD, a derivativethereof, or a similar type device to a donating vessel, drawing bloodfrom the donating vessel, and pumping it into the peripheral acceptingvein for a sufficient amount of time to cause a desired amount ofpersistent increase in the overall diameter and the lumen diameter ofthe peripheral vein. The blood pump may be implanted into the patient orit may remain external to the patient. When the pump is external to thepatient, it may be affixed to the patient for continuous pumping.Alternatively, the pump may be configured to detach from the donatingand accepting vessels of the patient for periodic and/or intermittentpumping sessions.

The lumen diameter of peripheral accepting veins can be monitored whilethe blood is being pumped into the vein using conventional methods suchas visualization with ultrasound or diagnostic angiography. Apump-conduit assembly or pump-catheter assembly may incorporate featuresthat facilitate diagnostic angiography such as radiopaque markers thatidentify sites that can be accessed with needle for injection ofcontrast into the assembly that will subsequently flow into theaccepting peripheral vein and make it visible during fluoroscopy usingboth conventional and digital subtraction angiography.

When a portion of a pump-conduit assembly or pump catheter assembly islocated external to the body, then an antimicrobial coating or cuff maybe affixed to the portion of the device that connects the implanted andexternal components. For example, when a controller and/or power sourceis strapped to the wrist, attached to a belt, or carried in a bag orpack, then the antimicrobial coating is placed on or around a connectionand/or entry point where the device enters the patient's body.

These and other objects, features, aspects and advantages of the presentinvention will become apparent to those skilled in the art from thefollowing detailed description, which, taken in conjunction with theannexed drawings, discloses preferred embodiments of the presentinvention.

BRIEF DESCRIPTION OF THE DRAWINGS

Referring now to the attached drawings which form a part of thisoriginal disclosure:

FIG. 1A is a schematic view of a pump-conduit assembly of a system andmethod in accordance with a first embodiment of the present invention;

FIG. 1B is a schematic view of the pump-conduit assembly of FIG. 1A asapplied to a circulatory system of a patient in accordance with thefirst embodiment of the present invention;

FIG. 1C is a magnified view of a portion of FIG. 1B;

FIG. 2A is a schematic view of a pump-conduit assembly of a system andmethod in accordance with a second embodiment of the present invention;

FIG. 2B is a schematic view of the pump-conduit assembly of FIG. 2A asapplied to a circulatory system of a patient in accordance with thesecond embodiment of the present invention;

FIG. 2C is a magnified view of a portion of FIG. 2B;

FIG. 3 is a schematic view of a pump-conduit assembly of a system andmethod as applied to a circulatory system of a patient in accordancewith a third embodiment of the present invention;

FIG. 4A is a schematic view of a pump-catheter assembly of a system andmethod in accordance with a fourth embodiment of the present invention;

FIG. 4B is a schematic view of the pump-catheter assembly of FIG. 4A asapplied to a circulatory system of a patient in accordance with thefourth embodiment of the present invention;

FIG. 5A is a schematic view of a pump-conduit assembly of a system andmethod in accordance with a fifth embodiment of the present invention;

FIG. 5B is a schematic view of the pump-conduit assembly of FIG. 5A asapplied to a circulatory system of a patient in accordance with thefifth embodiment of the present invention;

FIG. 6 is a schematic diagram of a pump operated in conjunction with acontrol unit for use in any of the above-mentioned embodiments;

FIG. 7 is a flow chart of a method in accordance with the first andthird embodiments of the present invention;

FIG. 8 is a flow chart of a method in accordance with the second andfourth embodiments of the present invention; and

FIG. 9 is a flow chart of a method in accordance with the fifthembodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Preferred embodiments of the present invention will now be explainedwith reference to the drawings. It will be apparent to those skilled inthe art from this disclosure that the following description of theembodiments of the present invention is provided for illustration onlyand not for limiting the invention as defined by the appended claims andtheir equivalents. Referring initially to FIGS. 1-4, a system 10 toincrease the overall diameter of veins is illustrated as used for apatient 20. The system 10 removes deoxygenated venous blood from thepatient's venous system 22 and redirects that blood into the acceptingperipheral vein 30. The system 10 also increases the speed of blood inthe accepting peripheral vein 30 and increases the WSS exerted on theendothelium of the accepting peripheral vein 30, to increase thediameter of the accepting peripheral vein 30 located, for example, in anarm 24 or a leg 26. The diameter of blood vessels such as peripheralveins can be determined by measuring the diameter of the lumen, which isthe open space at the center of blood vessel where blood is flowing. Forthe purpose of this application, this measurement is referred to as“lumen diameter”. The diameter of blood vessels can be determined bymeasuring the diameter in a manner that includes the wall of the bloodvessel. For the purpose of this application, this measurement isreferred to as “overall diameter”. The invention relates tosimultaneously and persistently increasing the overall diameter andlumen diameter of a peripheral vein by directing blood (preferably withlow pulsatility) into the peripheral vein, thereby increasing the speedof the blood in the peripheral vein and increasing the WSS on theendothelium of the peripheral vein. Systems and methods are describedwherein the speed of the blood in a peripheral vein and the WSS on theendothelium of the peripheral vein is increased by using a pump.Preferably, the pump directs blood into the peripheral vein, wherein thepumped blood has reduced pulsatility, such as when the pulse pressure islower than blood in a peripheral artery.

The systems and methods described herein increase the WSS level in aperipheral vein. Normal WSS for veins ranges between 0.076 Pa and 0.76Pa. The systems and methods described herein are configured to increasethe WSS level in the accepting peripheral vein to range from about 0.76Pa and 23 Pa, preferably to a range between 2.5 Pa and 7.5 Pa. SustainedWSS less than 0.76 Pa might dilate veins but at a rate that iscomparatively slow. Sustained WSS greater than 23 Pa are likely to causedenudation (loss) of the endothelium of the vein, which is known toretard dilation of blood vessels in response to increases in blood speedand WSS. Pumping blood in a manner that increases WSS to the desiredrange for preferably at least 7 days, and more preferably between about14 and 84 days, for example, produces an amount of persistent dilationin the accepting peripheral vein such that veins that were initiallyineligible for use as a hemodialysis access site or bypass graft due tosmall vein diameter become usable. The blood pumping process may bemonitored and adjusted periodically. For example, the pump may beadjusted every seven days to account for changes in the peripheral veinprior to achieving the desired persistent dilation.

The systems and methods described herein also increase the speed ofblood in peripheral veins and in certain instances, peripheral arteries.At rest, the mean speed of blood in the cephalic vein in humans isgenerally between 5-9 cm/s, while the speed of blood in the brachialartery is generally between 10-15 cm/s. For the systems and methodsdescribed herein, the mean speed of blood in the peripheral vein isincreased to a range between 15 cm/s-100 cm/s, preferably to a rangebetween 25 cm/s and 100 cm/s, depending on the diameter of peripheralaccepting vein and the length of time the pumping of blood into theperipheral accepting vein is planned. Preferably, the mean blood speedis increased for between 7 days and 84 days, or preferably between 7 and42 days, to induce persistent dilation in the peripheral accepting veinsuch that veins that were initially ineligible for use as a hemodialysisaccess site or bypass graft due to a small vein diameter become usable.This can also be accomplished by intermittently increasing mean bloodspeed during the treatment period, with intervening periods of normalmean blood speed.

Studies have shown hemodynamic forces and changes in hemodynamic forceswithin veins play a vital role in determining the overall diameter andlumen diameter of those veins. For example, persistent increases inblood speed and WSS can lead to vein dilation. The elevated blood speedand WSS are sensed by endothelial cells, which trigger signalingmechanisms that result in stimulation of vascular smooth muscle cells,attraction of monocytes and macrophages, and synthesis and release ofproteases capable of degrading components of the extracellular matrixsuch as collagen and elastin. As such, the present invention relates toincreasing blood speed and WSS for a period of time sufficient to resultin vein remodeling and dilation.

Assuming a Hagen-Poiseuille blood flow in the vessel (i.e. a laminarflow with a fully developed parabolic velocity profile), then WSS can bedetermined using the equation:WSS(τ)=4Qλ/πR ³, where:

-   -   Q=volume flow rate in mL/s    -   μ=viscosity of blood in units of poise    -   R=radius of vessel in cm    -   τ=wall shear stress in dynes/cm²

The systems and methods described herein increase the WSS level in aperipheral vein. Normal WSS for veins ranges between 0.076 Pa and 0.76Pa. The systems and methods described herein increase the WSS level to arange between 0.76 Pa and 23 Pa, preferably to a range between 2.5 Paand 7.5 Pa. Preferably, the WSS is increased for between 7 days and 84days, or preferably between 7 and 42 days, to induce persistent dilationin the peripheral accepting vein such that veins that were initiallyineligible for use as a hemodialysis access site or bypass graft due toa small vein diameter become usable. This can also be accomplished byintermittently increasing WSS during the treatment period, withintervening periods of normal WSS.

WSS levels in the accepting peripheral vein lower than 0.076 Pa maydilate veins however, this would likely occurs at a slow rate. WSSlevels in accepting peripheral veins higher than about 23 Pa are likelyto cause denudation (loss) of the endothelium of the veins. Denudationof the endothelium of blood vessels is known to retard dilation in thesetting of increased in blood speed and WSS. The increased WSS inducessufficient persistent dilation in the veins, such that those that wereinitially ineligible for use as a hemodialysis access site or bypassgraft due to a small diameter become usable. The diameter of theaccepting vein can be determined intermittently, such as every 7-14 daysfor example, to allow for pump speed adjustment in order to optimizevein dilation during the treatment period.

The systems and methods described herein also increase the speed ofblood in peripheral veins and in certain instances, peripheral arteries.At rest, the mean speed of blood in the cephalic vein in humans isgenerally between 5-9 cm/s, while the speed of blood in the brachialartery is generally between 10-15 cm/s. For the systems and methodsdescribed herein, the mean speed of blood in the peripheral vein isincreased to a range between 15 cm/s-100 cm/s, preferably to a rangebetween 25 cm/s and 100 cm/s, depending on the diameter of peripheralaccepting vein and the length of time the pumping of blood into theperipheral accepting vein is planned. Preferably, the mean blood speedis increased for between 7 days and 84 days, or preferably between 7 and42 days, to induce persistent dilation in the peripheral accepting veinsuch that veins that were initially ineligible for use as a hemodialysisaccess site or bypass graft due to a small vein diameter become usable.Mean blood speed levels in the accepting peripheral vein lower than 15cm/s may dilate veins however, this would likely occurs at a slow rate.Mean blood velocity levels in accepting peripheral veins higher thanabout 100 cm/s are likely to cause denudation (loss) of the endotheliumof the veins. Denudation of the endothelium of blood vessels is known toretard dilation in the setting of increased in blood speed. Theincreased mean blood speed induces sufficient persistent dilation in theveins, such that those that were initially ineligible for use as ahemodialysis access site or bypass graft due to a small diameter becomeusable. The diameter of the accepting vein can be determinedintermittently, such as every 7-14 days for example, to allow for pumpspeed adjustment in order to optimize vein dilation during the treatmentperiod.

Referring to FIGS. 1-3, the system 10 includes a pump-conduit assembly12 for directing deoxygenated venous blood from a donating vein 29 ofthe venous system 22 of the patient 20 to the peripheral or acceptingvein 30. In various embodiments, the peripheral or accepting vein 30 maybe a cephalic vein, radial vein, median vein, ulnar vein, antecubitalvein, median cephalic vein, median basilic vein, basilic vein, brachialvein, lesser saphenous vein, greater saphenous vein, or femoral vein.Other veins that might be useful in the creation of a hemodialysisaccess site or bypass graft or other veins useful for other vascularsurgery procedures requiring the use of veins may be used. Thepump-conduit assembly 12 delivers the deoxygenated blood to theperipheral or accepting vein 30. The rapid speed of the blood 34 and theelevated WSS in the peripheral vein 30 causes the peripheral oraccepting vein 30 to enlarge over time. Thus, the system 10 and method100 (referring to FIGS. 7-9) of the present invention advantageouslyincreases the diameter of the peripheral or accepting vein 30 so that itcan be used, for example, to construct an AVF or AVG access site forhemodialysis or as a bypass graft.

As used herein, deoxygenated blood is blood that has passed through thecapillary system and had oxygen removed by the surrounding tissues andthen passed into the venous system 22. A peripheral vein 30, as usedherein, means any vein with a portion residing outside of the chest,abdomen, or pelvis. In the embodiment shown in FIGS. 1A and 2A, theperipheral or accepting vein 30 is the cephalic vein. However, in otherembodiments, the peripheral vein 30 may be a radial vein, median vein,ulnar vein, antecubital vein, median cephalic vein, median basilic vein,basilic vein, brachial vein, lesser saphenous vein, greater saphenousvein, or femoral vein. In addition to a peripheral vein, other veinsthat might be useful in the creation of a hemodialysis access site orbypass graft or other veins useful for other vascular surgery proceduresrequiring the use of veins may also be used, such as those residing inthe chest, abdomen, and pelvis.

In order to reduce pulsatility and/or provided low-pulsatile flow, anumber of pulsatility dampening techniques may be used. By way ofexample, and not limitation, such techniques include tuning thehead-flow characteristics of a blood pump, adding compliance to the pumpoutflow, and/or modulating the pump speed.

An AVF created using the cephalic vein at the wrist is a preferred formof vascular access for hemodialysis but this vein is frequently ofinadequate diameter to facilitate the creation of an AVF in thislocation. Thus, the present invention is most advantageous to creatingwrist AVFs in ESRD patients and increasing the percentage of ESRDpatients that receive hemodialysis using a wrist AVF as a vascularaccess site.

The pump-conduit assembly 12 includes a blood pump 14 and syntheticconduits 16 and 18, i.e. an inflow conduit 16 and an outflow conduit 18.Blood pumps have been developed as a component of ventricular assistdevices (VADs) and have been miniaturized to treat both adult patientswith moderate heart failure and pediatric patients. These pumps can beimplanted or remain external to the patient and are usually connected toa controller and a power source. Referring to FIG. 6, a schematicdiagram of the pump-conduit assembly 12 is illustrated. The pump 14 canbe a rotary pump such as an axial, mixed flow, or centrifugal pump.Without recognizing specific limitations, the bearing for the pump 14can be constructed with magnetic fields, with hydrodynamic forces, orusing a mechanical contact bearing such as a double-pin bearing. Pumpsused in pediatric VAD systems or other low flow VAD systems can be used.Alternatively, the pump 14 can be an extracardiac pump such as thatshown and described in U.S. Pat. Nos. 6,015,272 and 6,244,835, both ofwhich are hereby incorporated herein by reference. These pumps aresuitable for use in the system 10 and method 100 of the presentinvention. The pump 14 has an inlet 38 to receive deoxygenated blooddrawn through the inflow conduit 16 and an outlet 40 for blood flow 34to exit the pump 14. In regards to pumps used in pediatric VAD systemsor other low flow VAD systems suitable for use as pump 14 of the presentinvention, these pumps can be sized as small as about the size of a AAbattery or the diameter of a United States half dollar or quarter, andcan weigh as little as about 25-35 g or less. These pumps are designedto pump about 0.3 to 1.5 L/min or 1 to 2.5 L/min, for example.Modifications to these pumps could be made to reduce this range to aslow as 0.05 L/min for use in small diameter veins. A priming volume canbe about 0.5-0.6 ml, for example. The blood-contacting surfaces of thepump 14 preferably include Ti₆Al₄V and commercially pure titanium alloysand can include other materials such as injection-moldable ceramics andpolymers, and alternative titanium alloys, e.g. Ti₆Al₇Nb. Theblood-contacting surface also preferably has one or more coatings andsurface treatments. As such, any of a variety of pumping devices can beused so long as it can be connected to the vascular system and can pumpa sufficient amount of blood such that the desired WSS is achieved inthe accepting vein.

The pump 14 includes various components 42 and a motor 44, as shown inFIG. 6. The various components 42 and motor 44 can be those common to aVAD. For example, the components 42 include one or more of a shaft,impeller blades, bearings, stator vanes, rotor, or stator. The rotor canbe magnetically levitated. The motor 44 can include a stator, rotor,coil, and magnets. The motor 44 may be any suitable electric motor, suchas a multi-phase motor controlled via pulse-width modulated current.

The system 10 and method 100 can utilize one or more of the pumpsdescribed in the following publications: The PediaFlow™ PediatricVentricular Assist Device, P. Wearden, et al., Pediatric Cardiac SurgeryAnnual, pp. 92-98, 2006; J. Wu et al., Designing with Heart, ANSYSAdvantage, Vol. 1, Iss. 2, pp. s12-s13, 2007; and J. Baldwin, et al.,The National Heart, Lung, and Blood Institute Pediatric CirculatorySupport Program, Circulation, Vol. 113, pp. 147-155, 2006. Otherexamples of pumps that can be used as the pump 14 include: the Novacor,PediaFlow, Levacor, or MiVAD from World Heart, Inc.; the Debakey HeartAssist 1-5 from Micromed, Inc.; the HeartMate XVE, HeartMate II,HeartMate III, IVAD, or PVAD from Thoratec, Inc.; the Impella, BVS5000,AB5000, or Symphony from Abiomed, Inc.; the TandemHeart fromCardiacAssist, Inc.; the VentrAssist from Ventracor, Inc.; the Incor orExcor from Berlin Heart, GmbH; the Duraheart from Terumo, Inc.; the HVADor MVAD from HeartWare, Inc.; the Jarvik 2000 Flowmaker or PediatricJarvik 2000 Flowmaker from Jarvik Heart, Inc.; the Gyro C1E3 fromKyocera, Inc.; the CorAide or PediPump from the Cleveland ClinicFoundation; the MEDOS HIA VAD from MEDOS Medizintechnik AG; the pCASfrom Ension, Inc; the Synergy from Circulite, Inc; the CentriMag,PediMag, and UltraMag from Levitronix, LLC; and, the BP-50 and BP-80from Medtronic, Inc. The pumps can be monitored and adjusted manually orwith a software program, application, or other automated system. Thesoftware program can automatically adjust the pump speed to maintain thedesired amount of blood flow and WSS in the accepting vein.Alternatively, the vein diameter and blood flow may be periodicallychecked manually and the pump may be manually adjusted, for example, bytuning the head-flow characteristics of the pump, adding compliance tothe pump outflow, and/or modulating the pump speed. Other adjustmentsmay also be made.

The synthetic conduits 16 and 18 are comprised of PTFE and/or Dacron,preferentially reinforced so that the synthetic conduits 16 and 18 areless susceptible to kinking and obstruction. All or a portion of theconduits 16 and 18 may be comprised of materials commonly used to makehemodialysis catheters such as polyvinyl chloride, polyethylene,polyurethane, and/or silicone. The synthetic conduits 16 and 18 can beof any material or combination of materials so long as the conduits 16and 18 exhibit necessary characteristics, such as flexibility,sterility, resistance to kinking, and can be connected to a blood vesselvia an anastomosis or inserted into the lumen of a blood vessel, asneeded. In addition, the synthetic conduits 16 and 18 preferably exhibitthe characteristics needed for tunneling (as necessary) and have luminalsurfaces that are resistant to thrombosis. As another example, thesynthetic conduits 16 and 18 can have an exterior layer composed of adifferent material than the luminal layer. The synthetic conduits 16 and18 can also be coated with silicon to aid in removal from the body andavoid latex allergies. In certain embodiments, the connection betweenthe synthetic conduit 16 or 18 and the vein 29 or 30 is made using aconventional surgical anastomosis, using suture in a running or dividedfashion, henceforth described as an “anastomotic connection.” Ananastomotic connection can also be made with surgical clips and otherstandard ways of making an anastomosis.

Referring to FIGS. 1-3, the synthetic inflow conduit 16 has a first end46 configured to fluidly connect to a donating vein 29 or the rightatrium 31 of the heart and a second end 48 connected to the inlet 38 ofthe pump 14. The donating vein 29 can include an antecubital vein,basilic vein, brachial vein, axillary vein, subclavian vein, jugularvein, brachiocephalic vein, superior vena cava, lesser saphenous vein,greater saphenous vein, femoral vein, common iliac vein, external iliacvein, superior vena cava, inferior vena cava, or other veins capable ofproviding sufficient blood flow to the pump for the purpose of causingpersistent dilation of the accepting peripheral vein. The syntheticoutflow conduit 18 has a first end 52 configured to fluidly connect tothe peripheral accepting vein 30 and a second end 54 connected to theoutlet 40 of the pump 14. The pump-conduit assembly 12 is configured toredirect blood from the donating vein 29 to the peripheral acceptingvein 30 in a manner that increases the blood speed and WSS in theperipheral vein to the desired level for a period of time sufficient tocause a persistent increase in the overall diameter and lumen diameterof the peripheral vein. In certain embodiments, a portion of thesynthetic conduits 16, 18 may be extracorporeal to the patient 20.Referring to FIGS. 1 and 3, the first end 46 of the inflow conduit 16and the first end 52 of the outflow conduit 18 are configured for ananastomotic connection. As shown in FIGS. 1B and 1C, the first end 46 isfluidly connected to the internal jugular vein (which serves as thedonating vein 29) via an anastomotic connection and the first end 52 ofthe outflow conduit 18 is fluidly connected to the cephalic vein (whichserves as the peripheral accepting vein 30) via an anastomoticconnection.

Referring to FIGS. 2A-2C, the first end 46 of the synthetic inflowconduit 16 is configured as a catheter. The fluid connection between thesynthetic inflow conduit 16 and the venous system is made by positioningthe tip of the catheter portion 50 of the synthetic inflow conduit intothe superior vena cava 27, henceforth described as a “catheterconnection”. When a catheter connection is made with a donating vein 29(in this case, the superior vena cava 27), the catheter portion 50 ofthe synthetic inflow conduit 46 may enter the venous system at anylocation where the vein lumen diameter is adequate to accept thecatheter portion 50. The tip of the catheter portion 50 may be placed atany location where sufficient blood can be drawn into the catheter toprovide the desired blood flow 34 to the accepting vein 30. Preferredlocations for the tip of the catheter portion 50 include, but are notlimited to a brachiocephalic vein, the superior vena cava 27, and theright atrium 31. In the embodiment illustrated in FIGS. 2B-2C, thesystem 10 draws deoxygenated blood from the superior vena cava 27 of thepatient 20 and redirects it to the cephalic vein 30 in the arm 24.

In another embodiment shown in FIG. 3, the system 10 redirectsdeoxygenated venous blood from donating vein 29 (in this case, the morecentral portion of the greater saphenous vein) to the peripheralaccepting vein 30 (in this case, a more peripheral portion of thegreater saphenous vein) in the leg 26 thereby increasing the speed ofblood and WSS in the accepting vein to the desired level and for aperiod of time sufficient to cause a persistent increase in the lumendiameter and overall diameter of the accepting greater saphenous vein30. In the embodiment shown in FIG. 3, the inflow conduit 16 is fluidlyconnected to a greater saphenous vein 29 of the patient 20 via ananastomotic connection. In some embodiments, the blood is pumped intothe accepting vein with a pulsatility that is reduced when compared withthe pulsatility of blood in a peripheral artery. For example, the meanpulse pressure in the accepting vein adjacent to the connection with theoutflow conduit is <40 mmHg, <30 mmHg, <20 mmHg, <10 mmHg, or preferably<5 mmHg with the pump operating. The pumping of blood into theperipheral vein and the increase in blood speed and WSS continues for aperiod of time sufficient to cause a persistent increase in the overalldiameter and lumen diameter of the accepting greater saphenous veinsegment 30 to facilitate extraction and autotransplantation as part of asurgery to create a cardiac or peripheral bypass graft, or other surgerythat requires autotransplantation of a portion of a patient's vein.

Referring to FIG. 4A, in another embodiment, an extracorporeal pump 114is attached to two specialized catheters, an inflow catheter 55, and anoutflow catheter 56 to form a catheter-pump assembly 13. The pump 114draws deoxygenated blood into the lumen of the inflow catheter 55 fromthe donating vein 29 and then discharges the blood from the outflowcatheter 56 and into the lumen of the peripheral accepting vein 30,thereby increasing the speed of blood and the WSS in the peripheralaccepting vein 30.

FIGS. 4A and 4B illustrate another embodiment of the system 10. Thepump-catheter assembly 13 is configured to increase the blood speed andWSS in vein segment d. The inflow catheter 55 and the outflow catheter56 may optionally be joined in all or some portions (such as with adouble lumen catheter) and can be percutaneously inserted into the lumenof the accepting peripheral vein 30, obviating the need for an invasivesurgical procedure. For this embodiment, a portion of the catheter canbe tunneled subcutaneously before exiting the skin in order to reducethe risk of infection. Extracorporeal portions of the catheters 119 and120 and the extracorporeal pump 114 can be affixed to the body,connected to a power source, and operated in a manner that increases thespeed of the blood 34 and WSS in segment d of the accepting peripheralvein 30 for a period of time sufficient to cause a persistent increasethe overall diameter and lumen diameter of segment d of the acceptingperipheral vein 30. Once the desired amount of diameter enlargement hasoccurred in segment d of the accepting peripheral vein 30, thepump-catheter assembly 12 is removed and a surgical procedure can beperformed to create a hemodialysis access site or bypass graft using atleast a portion of the enlarged segment d of the accepting peripheralvein 30, either at the same time or in a subsequent operation.

Referring to FIGS. 5A and 5B, a system 10 to increase the overalldiameter of veins is illustrated as used for a patient 20. The system 10removes oxygenated arterial blood from a patient's peripheral artery 221and redirects that blood into the accepting peripheral vein 30 and isconfigured and operated to increase the blood speed and WSS in theaccepting peripheral vein 30 for a period of time sufficient to cause apersistent increase in the diameter of the accepting peripheral vein 30in, for example, an arm 24 or a leg 26. An embodiment of a system 10 inwhich a pump 214 is implanted in the arm 24 is illustrated. The pump 214has an inlet 216 connected to an artery 221 in the arm 24 viaanastomotic connection. The pump 214 also has an outlet 218 connected tothe peripheral vein 30 via an anastomotic connection. The pump 214 iscontrolled and powered by the control unit 58. In operation, the pump214 withdraws blood from the artery 221 and pumps the blood into theperipheral vein 30. This embodiment can allow the performance of asurgical procedure that avoids the need for extended synthetic conduitsand increases blood speed and WSS in both the peripheral vein 30 and theperipheral artery 221 resulting in, if operated for a sufficient periodof time, simultaneous dilation of the vein 30 and the artery 221.Specifically, the pump 214 is implanted in the forearm of the patient20. Once the desired amount of diameter enlargement has occurred in theaccepting peripheral vein 30, the pump 214 can be removed and a surgicalprocedure can be performed to create a hemodialysis access site orbypass graft using at least a portion the enlarged artery 221 or vein30, either at that time or during a subsequent operation.

In various embodiments, oxygenated arterial blood may be drawn from adonating artery. Donating arteries may include, but are not limited to,a radial artery, ulnar artery, interosseous artery, brachial artery,anterior tibial artery, posterior tibial artery, peroneal artery,popliteal artery, profunda artery, superficial femoral artery, orfemoral artery.

Referring to FIG. 6, a schematic of an embodiment of the system 10 isillustrated. The control unit 58 is connected to the pump 14 and isconfigured to control the speed of the pump 14 and collect informationon the function of the pump 14. The control unit 58 may be implanted inthe patient 20, may remain external to the patient 20, or may haveimplanted and external portions. A power source is embodied in a powerunit 60 and is connected to the control unit 58 and the pump 14. Thepower unit 60 provides energy to the pump 14 and the control unit 58 forroutine operation. The power unit 60 may be implanted in the patient 20,may remain external to the patient 20, or may have implanted andexternal portions. The power unit 60 may include a battery 61. Thebattery 61 is preferably rechargeable and is recharged via a connector69 to an AC source. Such rechargeable batteries could also be rechargedusing lead wires or via transcutaneous energy transmission. Optionally,the connector 69 may deliver electrical power to the power unit 60without the aid of the battery 61. It will be apparent to one ofordinary skill in the art from this disclosure that the control unit 58can be configured to utilize alternative power-control systems.

Sensors 66 and 67 may be incorporated into the synthetic conduits 17 and18, the pump 14, or the control unit 58. The sensors 66 and 67 areconnected to the control unit 58 via cable 68 or can wirelesslycommunicate with the control unit 58. The sensors 66 and 67 can monitorblood flow, blood speed, intraluminal pressure, and resistance to flowand may send signals to the control unit 58 to alter pump speed. Forexample, as the peripheral vein 30 receiving the pumped blood dilates,blood speed in the vein decreases, along with resistance to blood flow34 from the outflow conduit 18. In order to maintain the desired bloodspeed and WSS, the pump speed must be adjusted as the peripheral vein 30dilates over time. The sensors 66 and 67 may sense blood speed in theperipheral vein 30 or resistance to blood flow and then signal thecontrol unit 58 which then increases the speed of the pump 14accordingly. Thus, the present invention advantageously provides amonitoring system, constituted by the control unit 58 and sensors 66 and67, to adjust the pump speed to maintain the desired blood speed and WSSin the accepting peripheral vein 30 as it dilates over time.Alternatively, the control unit may rely on a measurement, including aninternal measurement of the electrical current to the motor 44 as abasis for estimating blood flow, blood speed, intraluminal pressure, orresistance to flow, thus obviating the need for sensors 66 and 67. Thecontrol unit 58 may also include manual controls to adjust pump speed orother pumping parameters.

The control unit 58 is operatively connected to the pump-conduitassembly 12. Specifically, the control unit 58 is operatively connectedto the pump 14 by one or more cables 62. Utilizing the power unit 60,the control unit 58 preferably supplies pump motor control current, suchas pulse width modulated motor control current to the pump 14 via cable62. The control unit 58 can also receive feedback or other signals fromthe pump 14. The control unit 58 further includes a communication unit64 that is utilized to collect data and communicate the data, viatelemetric transmission, for example. Furthermore, the communicationunit 64 is configured to receive instructions or data for reprogrammingthe control unit 58. Therefore, the communication unit 64 is configuredto receive instructions or data for controlling the pump 14.

The present invention advantageously provides a monitoring system,constituted by the control unit 58 and sensors 66 and 67, to adjust theoperation of the pump to maintain the desired blood speed and WSS in theaccepting peripheral vein 30 as it dilates over time.

Preferably, the pump 14 is configured to provide a blood flow 34 in arange from about 50-1500 mL/min, for example, and increase the WSS in anaccepting peripheral vein to a range of between 0.76 Pa and 23 Pa,preferably to a range between 2.5 Pa and 7.5 Pa. The pump 14 isconfigured to maintain the desired level of blood flow and WSS in theaccepting peripheral vein 30 for a period of about 7-84 days, forexample, and preferably about 14-42 days, for example. In certainsituations where a large amount of vein dilation is desired or wherevein dilation occurs slowly, the pump 14 is configured to maintain thedesired level of blood flow and WSS in the accepting peripheral vein 30for longer than 42 days.

The pump-conduit assembly 12 can be implanted on the right side of thepatient 20, or can be implanted on the left side, as need be. Thelengths of the conduits 16 and 18 can be adjusted for the desiredplacement. Specifically for FIGS. 1B and 1C, the first end 46 of theinflow conduit 16 is fluidly connected to the location 29 in the rightinternal jugular vein 29 and the first end 52 of the outflow conduit 18is fluidly connected to the cephalic vein 30 in the right forearm.Specifically for FIGS. 2B and 2C, the first end 46 of the inflow conduit16 is fluidly connected to the location 29 in the superior vena cava 27and the first end 52 of the outflow conduit 18 is fluidly connected tothe cephalic vein 30 in the right forearm 24. After connection, pumpingis started. That is, the control unit 58 begins to operate the motor 44.The pump 14 pumps blood 34 through the outlet conduit 18 and into theperipheral vein 30. The control unit 58 adjusts pumping over the courseof time by utilizing data provided by the sensors 66 and 67. FIGS. 1-4illustrate examples in which the system 10 pumps deoxygenated blood.FIG. 5 illustrates an example in which the system 10 pumps oxygenatedblood. In some embodiments, the blood is pumped into the accepting veinwith a pulsatility that is reduced when compared with the pulsatility ofblood in a peripheral artery. For example, the mean pulse pressure inthe accepting vein is <40 mmHg, <30 mmHg, <20 mmHg, <10 mmHg, orpreferably <5 mmHg with the pump operating and delivering blood into theperipheral vein. In other embodiments, the blood is pumped into theaccepting vein with a pulsatility that is equal to or increased whencompared with the pulsatility of blood in a peripheral artery. For theseembodiments, the mean pulse pressure in the accepting vein adjacent tothe connection with the outflow conduit is ≧40 mmHg with the pumpoperating.

In one specific embodiment illustrated in FIGS. 1B and 1C, the donatingvein 29 is a jugular vein 21, preferentially an internal jugular vein21. The internal jugular vein 21 is particularly useful as a donatingvein 29 due to the absence of valves between the internal jugular vein21 and the right atrium 31, which would allow the synthetic inflowconduit 16 to be able to draw a large volume of deoxygenated blood perunit time. The inflow conduit 18 is fluidly connected to the internaljugular vein 21 of the patient 20. Deoxygenated blood is drawn from theinternal jugular vein 21 and pumped into the peripheral accepting vein30 in the arm 24 or leg 26 resulting in an increase in the speed ofblood 34 and WSS in the peripheral accepting vein. In some embodiments,the blood is pumped into the accepting vein with a pulsatility that isreduced when compared with the pulsatility of blood in a peripheralartery. For example, the mean pulse pressure in the accepting veinadjacent to the connection with the outflow conduit is <40 mmHg, <30mmHg, <20 mmHg, <10 mmHg, or preferably <5 mmHg with the pump operating.

As noted previously, FIG. 5B illustrates an example in which the system10 draws oxygenated blood. The inflow conduit 216 is fluidly connectedto the radial artery 221 of the patient 20 and the outflow conduit 218is fluidly connected to the cephalic vein, both using an anastomoticconnection. Thus, oxygenated blood is drawn from the radial artery 221and pumped into the cephalic vein 30 in the arm 24 in a manner thatresults in an increased blood speed and WSS in the cephalic vein for asufficient period of time to cause a persistent increase in the overalldiameter and lumen diameter of the accepting peripheral vein. In someembodiments, the blood is pumped into the accepting vein with apulsatility that is reduced when compared with the pulsatility of bloodin a peripheral artery. For example, the mean pulse pressure in theaccepting vein adjacent to the connection with the outflow conduit is<40 mmHg, <30 mmHg, <20 mmHg, <10 mmHg, or preferably <5 mmHg with thepump operating and delivering blood into the peripheral accepting vein.

Referring to FIGS. 7-9, various embodiments of the method 100 increasethe overall diameter and the lumen diameter of the peripheral vein 30.As shown in FIG. 7, a physician or surgeon performs a procedure toaccess a vein or artery and connects a pump to establish fluidcommunication with a vein carrying deoxygenated blood at step 101. Atstep 102, the pump is connected to a peripheral vein. In thisembodiment, the pump-conduit assembly 12 is preferably implanted in theneck, chest and the arm 24 of the patient 20. In another embodiment,wherein the peripheral vein 30 is the saphenous vein 36, thepump-conduit assembly 12 is implanted in the leg 26. In one example, thephysician fluidly connects the first end 46 of the pump-conduit assembly12 to the donating vein 29 and the second end of the pump-conduitassembly 12 to the peripheral accepting vein 30, utilizing a tunnelingprocedure (as necessary) to connect the two locations subcutaneously. Atstep 103, the deoxygenated blood is pumped into the peripheral acceptingvein. At step 104, the pumping continues for a period of time, while thephysician waits for the peripheral accepting vein to dilate. In oneembodiment, after the pump is turned on to start the pumping ofdeoxygenated blood, the skin incisions are closed, as necessary.

In another embodiment, portions of the synthetic conduits 16 and 18and/or the pump 14 are extracorporeally located. In this embodiment, thepump 14 is then started and controlled via the control unit 58 to pumpthe deoxygenated blood through the pump-conduit assembly 12 and into theperipheral accepting vein 30 in a manner that increases the blood speedand WSS in the peripheral vein 30. The pumping process is monitoredperiodically and the control unit 58 is used to adjust the pump 14, inresponse to changes in the peripheral accepting vein 30. With periodicadjustments, as necessary, the pump continues to operate for an amountof time sufficient to result in the persistent dilation of the overalldiameter and lumen diameter of the peripheral vein 30. In a subsequentprocedure, the pump-conduit assembly 12 is disconnected and removed atstep 105. At step 106, the persistently dilated peripheral vein 30 isused to create an AVF, AVG, or bypass graft.

In another embodiment of the method 100, as shown in FIG. 8, thephysician or surgeon inserts one or more catheter portions 50 of thepump-catheter assembly into the venous system and positions them in adonating vessel and a peripheral vein 30 at step 107. At step 108, thepump is operated to pump deoxygenated blood into the deoxygenated blood.The physician then waits for the peripheral vessel to dilate at step109. The pump-catheter assembly is removed and the persistently dilatedvein is used to create an AVF, AVG, or bypass graft, at steps 110 and111, respectively.

FIG. 9 shows, yet another embodiment of the method 100. At step 112, aphysician or surgeon performs a procedure to access a vein and connectsa pump to establish fluid communication with a peripheral vein. At step113, the pump is connected to a peripheral artery. The pump is operated,at step 114 to pump oxygenated blood from the peripheral artery to theperipheral vein. At step 115, the pumping continues for a period oftime, while the physician waits for the peripheral vein dilate. At step116, the pump is removed and at step 117, the persistently dilated veinis used to create an AVF, AVG, or bypass graft.

In various embodiments, the method 100 and/or the system 10 may be usedto in periodic and/or intermittent sessions, as opposed to continuoustreatment. Typically, hemodialysis treatments that may last from 3 to 5hours are given in a dialysis facility up to 3 times a week. Therefore,various embodiments of the system 10 and method 100 may be used toprovide blood pumping treatments on a similar schedule over a 4 to 6week period. The treatments may be performed in any suitable location,including in an outpatient setting.

In one embodiment, the blood pumping treatment is done intermittently inconjunction with hemodialysis treatments. In this embodiment, a low-flowpump, a standard in-dwelling hemodialysis catheter functioning as aninflow catheter, and a minimally traumatic needle or catheter placed inthe peripheral vein to function as an outflow catheter may be used. Anumber of continuous flow blood pumps operated from a bedside console[e.g. catheter-based VADs and pediatric cardiopulmonary bypass (CPB) orextracorporeal membrane oxygenation (ECMO) pumps] may be easily adaptedfor use with the method 100.

In various embodiments where the blood pumping occurs through periodicpumping sessions, the access to the blood vessels may also occur throughone or more ports or surgically created access sites. By way of exampleand not limitation, the access may be achieved through a needle, aperipherally inserted central catheter, a tunneled catheter, anon-tunneled catheter, and/or a subcutaneous implantable port.

In another embodiment of the system 10, a low-flow pump is used toincrease WSS and blood speed in a blood vessel. The low-flow pump has aninlet conduit fluidly connected to a blood vessel and an outlet conduitfluidly connected to a vein pumps blood from the blood vessel to thevein for a period between about 7 days and 84 day. The low-flow pumppumps blood such that the wall shear stress of the vein ranges betweenabout 0.076 Pa to about 23 Pa. The low-flow pump also includes anadjustment device. The adjustment device may be in communication with asoftware-based automatic adjustment system or the adjustment device mayhave manual controls. The inlet conduit and the outlet conduit may rangein length from about 10 centimeters to about 107 centimeters.

The present invention also relates to a method of assembling andoperating a blood pump system, including various embodiments of thepump-conduit system 10. The method includes attaching a first conduit influid communication with the pump-conduit system 10 to an artery andattaching a second conduit in fluid communication with the pump-conduitsystem to a vein. The pump-conduit system 10 is then activated to pumpblood between the artery and the vein.

In understanding the scope of the present invention, the term“comprising” and its derivatives, as used herein, are intended to beopen ended terms that specify the presence of the stated features,elements, components, groups, integers, and/or steps, but do not excludethe presence of other unstated features, elements, components, groups,integers and/or steps. The foregoing also applies to words havingsimilar meanings such as the terms, “including”, “having”, and theirderivatives. The terms of degree such as “substantially”, “about” and“approximate” as used herein mean a reasonable amount of deviation ofthe modified term such that the end result is not significantly changed.For example, these terms can be construed as including a deviation of atleast ±5% of the modified term if this deviation would not negate themeaning of the word it modifies.

While only selected embodiments have been chosen to illustrate thepresent invention, it will be apparent to those skilled in the art fromthis disclosure that various changes and modifications can be madeherein without departing from the scope of the invention as defined inthe appended claims. For example, the size, shape, location, ororientation of the various components can be changed as needed and/ordesired. Components that are shown directly connected or contacting eachother can have intermediate structures disposed between them. Thefunctions of one element can be performed by two, and vice versa. Thestructures and functions of one embodiment can be adopted in anotherembodiment. It is not necessary for all advantages to be present in aparticular embodiment at the same time. Every feature that is uniquefrom the prior art, alone or in combination with other features, alsoshould be considered a separate description of further inventions by theapplicant, including the structural and/or functional concepts embodiedby such features. Thus, the foregoing descriptions of the embodimentsaccording to the present invention are provided for illustration only,and not for limiting the invention as defined by the appended claims andtheir equivalents.

What is claimed is:
 1. A method for creating an arteriovenous fistula oran arteriovenous graft in a human patient, the method comprising:fluidly connecting one end of a pump-conduit assembly to a donatingvein; fluidly connecting another end of the pump-conduit assembly to anaccepting vein; pumping deoxygenated blood from the donating vein intothe accepting vein for at least 7 days, wherein: a) the pumping of bloodresults in a wall shear stress in the accepting vein of greater than orequal to 0.76 Pa, b) the pumping of blood results in a mean pulsepressure in the accepting vein of less than 20 mmHg, and c) the pumpingof blood results in an increase in overall diameter of the peripheralvein which persists after pumping has ceased and the pump-conduitassembly has been removed; and, creating the arteriovenous fistula orarteriovenous graft in the patient using at least a portion of theaccepting vein with the persistently-increased overall diameter.
 2. Themethod of claim 1, wherein the patient is in need of an arteriovenousfistula or arteriovenous graft for hemodialysis.
 3. The method of claim1, wherein the pump-conduit assembly pumps blood at a rate between 50ml/min and 1500 ml/min.
 4. The method of claim 1, wherein thepump-conduit assembly pumps blood at a rate between 100 ml/min and 1000ml/min.
 5. The method of claim 1, wherein a wall shear stress in theaccepting vein is between 0.76 Pa and 23 Pa when the pump-conduitassembly is in operation.
 6. The method of claim 1, wherein a wall shearstress in the accepting vein is between 2.5 Pa and 10 Pa when thepump-conduit assembly is in operation.
 7. The method of claim 1, whereina speed of the blood in the accepting vein is between 15 cm/s and 100cm/s when the pump-conduit assembly is in operation.
 8. The method ofclaim 1, wherein blood is pumped through the pump-conduit assembly forbetween 7 days and 42 days.
 9. The method of claim 1 further comprising:determining the overall diameter of the accepting vein and blood flowthrough the accepting vein after pumping the blood; and, changing aspeed of a pump portion of the pump-conduit assembly in order tomaintain a desired wall shear stress or blood speed in the acceptingvein.
 10. The method of claim 1, wherein a pulse pressure of the bloodin the accepting vein adjacent to a connection between the acceptingvein and the pump-conduit assembly is less than 10 mmHg when thepump-conduit assembly is in operation.
 11. The method of claim 1,wherein a pulse pressure of the blood in the accepting vein adjacent toa connection between the accepting vein and the pump-conduit assembly isless than 5 mmHg when the pump-conduit assembly is in operation.
 12. Themethod of claim 1, wherein the blood is pumped through the pump-conduitassembly for a distance of between 20 cm and 200 cm.
 13. The method ofclaim 1, wherein the donating vein is selected from a group consistingof a right atrium, a superior vena cava, an inferior vena cava, abrachiocephalic vein, a jugular vein, a subclavian vein, an axillaryvein, a common iliac vein, an external iliac vein, or a femoral vein.14. The method of claim 1, wherein the accepting vein is selected from agroup consisting of a cephalic vein, an ulnar vein, an antecubital vein,a basilic vein, a brachial vein, a lesser saphenous vein, a greatersaphenous vein, or a femoral vein.
 15. The method of claim 1, wherein apump portion of the pump-conduit assembly is implanted in the patient.16. The method of claim 1, wherein a pump portion of the pump-conduitassembly remains extracorporeal to the patient.
 17. The method of claim1, wherein the persistently-increased overall diameter of the acceptingvein is at least 2.5 mm.
 18. The method of claim 1, wherein thepersistently-increased overall diameter of the accepting vein is atleast 4.0 mm.
 19. The method of claim 1, wherein a pulse pressure of theblood in the accepting vein adjacent to a connection between theaccepting vein and the pump-conduit assembly is less than 5 mmHg whenthe pump-conduit assembly is in operation.